piperidines and Burns--Chemical

The aim of this study is to evaluate the anti-inflammatory and anti-fibrotic effects of halofuginone in caustic esophageal burn injury in rats.. Corrosive esophageal injury (CEI) was produced in male Wistar albino rats by instilling NaOH solution (1 ml, 37.5%) into the distal esophagus. Rats were decapitated on the 3rd day (early group) or 28th day (late group), and treated daily with either saline or halofuginone (100 µg/kg/day; i.p.), continued on alternate days after the third day. Histopathological evaluation and measurement of nitric oxide (NO), peroxynitrite (ONOO-) and oxygen-derived radicals by chemiluminescence (CL) were made in the distal 2 cm of the esophagus. Non-irrigated proximal esophageal samples were assessed for the levels of nuclear factor (NF)-κB, caspase-3, glutathione (GSH), malondialdehyde (MDA) and myeloperoxidase (MPO) activity.. GSH, MDA, NF-κB and caspase-3 levels, and MPO activity in the proximal esophagus were not different among groups. Increased number of TUNEL (+) cells in the irrigated esophagus of the early and late caustic injury groups was reduced by halofuginone treatment. High microscopic damage scores in both early and late CEI groups were decreased with halofuginone treatment. NO, ONOO- and CL levels, which were elevated in the saline-treated early CEI group, were reduced by halofuginone treatment, but reduced NO and ONOO- levels in the late period of saline-treated group were increased by halofuginone.. In addition to its anti-fibrotic effects, current findings demonstrate that halofuginone exerts antioxidant and anti-apoptotic actions and supports therapeutic potential for halofuginone in CEI-induced oxidative stress.

Topics: Animals; Anti-Inflammatory Agents; Apoptosis; Burns, Chemical; Caspase 3; Esophagus; Glutathione; Male; Malondialdehyde; NF-kappa B; Nitric Oxide; Oxidative Stress; Peroxidase; Piperidines; Quinazolinones; Rats; Rats, Wistar; Reactive Oxygen Species

To determine whether the inhibition of Substance P (SP) activity can reduce corneal neovascularization (CNV) by means of local administration of high-affinity, competitive, tachykinin 1 receptor (NK1R) antagonists Lanepitant and Befetupitant.. We performed a safety and efficacy study by using (1) two different C57BL/6 mouse models of CNV: alkali burn and sutures; (2) different concentrations; and (3) different routes of administration: topical or subconjunctival. Clinical examination endpoints, SP levels, CNV index, and leukocyte infiltration were measured.. Substance P increased after injury in the corneal epithelium of both CNV models, and later in the suture model. Topical Lanepitant was nontoxic to the ocular surface and effective in reducing hemangiogenesis and lymphangiogenesis, corneal SP levels, and leukocyte infiltration, as soon as 4 days later in the alkali burn model. Topical Lanepitant, up to 7 days, was ineffective in the suture model. However, subconjunctival Lanepitant was effective in reducing lymphatic CNV, leukocyte infiltration, and SP levels in the suture model, after 10 days. Additionally, in the alkali burn model, subconjunctival Lanepitant significantly reduced blood CNV, corneal perforation rate, opacity, and leukocyte infiltration, and improved tear secretion. Finally, topical application of Befetupitant reduced CNV in the alkali burn model but was toxic owing to the vehicle (dimethyl sulfoxide [DMSO]); hence, Befetupitant was not tested in the suture model.. The NK1R antagonist Lanepitant is safe for the ocular surface and effective in reducing both corneal hemangiogenesis and lymphangiogenesis, and leukocyte infiltration. We suggest that inhibition of NK1R may represent an adjunctive tool in the treatment of CNV.

Topics: Administration, Topical; Animals; Burns, Chemical; Conjunctiva; Cornea; Corneal Injuries; Corneal Neovascularization; Disease Models, Animal; Eye Burns; Female; Follow-Up Studies; Immunohistochemistry; Indoles; Injections; Mice; Mice, Inbred C57BL; Neurokinin-1 Receptor Antagonists; Ophthalmic Solutions; Piperidines; Pyridines; Receptors, Neurokinin-1; Sutures; Tomography, Optical Coherence; Treatment Outcome

A six-year old mixed-breed dog presented with severe trauma to the oral mucosa suggestive of chemical burn. Sixteen Harmonia axyridis (Coccinellidae) were removed from the oral cavity, which revealed trauma consistent with chemical burn. The beetles had become embedded in mucosa covering the hard palate and required manual removal. A diagnosis of beetle induced chemical burn was warranted and consistent with the nature of the chemical constituents of H. axyridis hemolymph.

Topics: Animals; Burns, Chemical; Coleoptera; Dog Diseases; Dogs; Hemolymph; Insect Bites and Stings; Mouth Mucosa; Piperidines; Tongue

Esophageal strictures caused by caustic injury continue to be a plaguing problem. Halofuginone (HF) has been proven to inhibit the formation of fibrosis in various animal models and human diseases. Its mechanism appears to be through the suppression of the production of collagen alpha1(I) and transforming growth factor-beta signaling pathway. We tried to assess whether HF would have an effect on the formation of strictures after inducing caustic esophageal.. Esophageal injury was caused by injecting 25% NaOH to an isolated esophageal segment. Study group rats were treated with HF orally for 3 consecutive days before the injury and afterward. Control group rats received regular chow. The results were evaluated by upper gastrointestinal series (UGI) and through pathologic studies.. HF treatment resulted in marked improvement in the esophageal strictures. The UGI series showed esophageal patency of 73% (45%-100%) in the treated animals (n = 7) as compared with almost no patency, 11% (5-16%), in the controls (n = 4) (P = .018). The histologic examination showed significantly less stricture and scarring in the treated group. Whereas the ratio between the esophageal wall thickness to mucosal thickness was 2.34 +/- 0.23 in the study group, the control group had a ratio of 9.56 +/- 0.69 (P = .0044). Finally, whereas 86% of the study group survived, all the rats in the control group died by day 20.. HF modulated the wound healing reaction caused by caustic injury of the esophagus in a rat model, resulting in increased esophageal patency, reduction in esophageal wall thickness, and increased survival.

Topics: Animals; Burns, Chemical; Caustics; Collagen Type I; Esophageal Stenosis; In Vitro Techniques; Piperidines; Protein Synthesis Inhibitors; Quinazolines; Quinazolinones; Radiography; Rats; Sodium Hydroxide; Transforming Growth Factor beta; Wound Healing

To assess the effects of halofuginone, a specific inhibitor of synthesis of collagen type 1, which is the major constituent of fibrosis, on esophageal stricture formation due to caustic ingestion.. Sixty rats were divided into four equal groups: control group; sham laparotomy group; caustic injury without treatment group; caustic injury with halofuginone treatment group. Caustic injuries were done by 50% sodium hydroxide. Halofuginone was administered by the first postoperative day. All animals were sacrificed on day 21; and the results were evaluated by hydroxyproline levels, stenosis index, lumen diameter, histopathological evaluation, wall thickness, and animal weights.. Mortality differences were significant comparing group 3 with group 1 and 2 (P = 0.006) and group 4 (P = 0.03). According to hydroxyproline levels, the differences are significantly higher (P <0.001) comparing group 3 with group 1, 2, and 4. The P value was considered significant in all other parameters (P <0.001) for all the groups but group 1 versus group 2 (P >0.05).. Halofuginone, a specific inhibitor of collagen type 1 synthesis, significantly reduced esophageal stricture occurrence.

Topics: Animals; Burns, Chemical; Caustics; Collagen Type I; Esophageal Stenosis; Esophagus; Fibrosis; Injections, Intraperitoneal; Male; Models, Animal; Piperidines; Protein Synthesis Inhibitors; Quinazolines; Quinazolinones; Rats; Rats, Sprague-Dawley; Sodium Hydroxide

Topics: Adult; Burns, Chemical; Dermatitis, Contact; Dermatitis, Occupational; Ethyl Chloride; Humans; Male; Necrosis; Penile Diseases; Piperidines; Scrotum; Sulfides

Topics: Adult; Alkaloids; Anti-Bacterial Agents; Anti-Infective Agents, Local; Bandages; Burns; Burns, Chemical; Burns, Electric; Child; Electrolytes; Eye Injuries; Facial Injuries; First Aid; Humans; Pain; Piperidines; Plasma Substitutes; Pyrazoles; Respiratory System; Shock; Tetanus; Transportation of Patients; Wounds and Injuries